Mandana Pouladzadeh, Fatemeh Khazaei, Saeid Bitaraf, Hossein Karimpourian, Mahsa Mombeyni, Mohammad-Reza Mahmoudian-Sani ,
Volume 83, Issue 4 (July 2025)
Abstract
Background: Breast cancer is the most prevalent malignancy among women and remains a leading cause of cancer-related mortality worldwide. Early detection can markedly improve patient survival, yet existing screening methods often lack sufficient accuracy and sensitivity. lncRNA KCNQ1OT1 has been implicated in the initiation and progression of tumors in several cancers, including breast cancer. This study aimed to evaluate the diagnostic potential of serum lncRNA KCNQ1OT1 expression as a biomarker for early detection of breast cancer.
Methods: This case-control study was conducted at Ahvaz Jundishapur University of Medical Sciences, Shafa Hospital, Ahvaz, Iran, between September 2024 and March 2025. Serum samples were obtained from 30 patients with histologically confirmed breast cancer and 30 healthy women serving as controls. Total RNA was extracted from 500 µL of serum, and cDNA was synthesized using oligo (dT) primers. Real-Time PCR was performed in triplicate, with GAPDH as the internal control. Relative gene expression was calculated using the 2^-ΔΔCt method, and data were analyzed using the Mann-Whitney U test and ROC analysis.
Results: The patient and control groups were homogeneous for most demographic parameters, but showed significant differences in age (P=0.023) and ethnicity (P=0.004). Most patients were in stage I of the disease. The median expression of serum KCNQ1OT1 was significantly lower in patients (0.024, IQR 0.013-0.033) than in controls (0.039, IQR 0.027-0.051), indicating marked downregulation in the patient group (P=0.0003). The ROC analysis yielded an AUC of 0.82 (95% CI: 0.67-0.96, SE=0.07, P=0.0005). At an optimal cutoff value of >0.031, the sensitivity was 70%, the specificity was 95%, and the positive likelihood ratio (LR⁺) ≈ was approximately 14, demonstrating strong discriminative ability.
Conclusion: Serum KCNQ1OT1 exhibits promising diagnostic performance for identifying early-stage breast cancer and may serve as a reliable noninvasive biomarker. Larger multicenter studies incorporating molecular subtyping and tissue correlation are required to validate its clinical applicability and strengthen diagnostic accuracy.
Samaneh Arab, Mohammad-Reza Mahmoudian-Sani , Najmeh Fattahi , Zakiye Ekhlasi, Samira Asgharzade,
Volume 83, Issue 5 (August 2025)
Abstract
Background: Retinal photoreceptor degeneration is a major cause of blindness. Stem cell therapies offer promise, and the miR-183/96/182 cluster, particularly miR-182 and miR-183, plays a crucial role in photoreceptor development and survival. Targeting these miRNAs may enhance human bone marrow–derived mesenchymal stem cells) hBMSCs (differentiation into photoreceptor-like cells, improving their therapeutic potential.
Methods: This in vitro study was conducted from April 2019 to March 2021 at the Clinical Biochemistry Research Center, Shahrekord University of Medical Sciences. hBMSCs were cultured in DMEM with fetal bovine serum and transfected with miR-182 and miR-183 mimics using Lipofectamine, with a scramble miRNA control. Transfection efficiency and miRNA overexpression were evaluated at 24 and 48 hours using real-time PCR. miRNA expression was normalised to Snord, while mRNA levels were normalised to GAPDH using the 2−ΔΔCt method. Photoreceptor-like differentiation was assessed by measuring the expression of retina-specific transcription factors and markers (OTX2, CRX, NRL, SLC1A1, PKCα, Recoverin, and RHO). Statistical analyses included the Shapiro–Wilk test for normality and the Mann-Whitney U test for group comparisons. Data were reported as Mean ± SEM, with 95% confidence intervals, and significance set at α = 0.05.
Results: Transfection of miR-182 and miR-183 significantly increased miRNA levels at 24–48 hours (P < 0.001) compared to the scramble control. This led to a marked upregulation of retinal-related genes, including CRX, OTX2, PKCα, Recoverin, NRL, and RHO, indicating activation of the photoreceptor gene network. Time-resolved analysis revealed stronger effects at 24–48 hours, supporting a transient window for pro-differentiation. RHO and CRX exhibited the most significant increases, while OTX2 and PKCα showed parallel rises, suggesting coordinated activation of early and intermediate photoreceptor programs. Scramble controls did not show comparable changes.
Conclusion: Transient overexpression of miR-182 and miR-183 in hBMSCs activates a photoreceptor-like gene expression program, promoting differentiation toward photoreceptor-like cells. This finding supports the potential use of miR-182/183 in stem cell-based therapies for retinal degeneration. Further studies should confirm protein expression, functional outcomes, and in vivo efficacy.
